Millions of Americans suffer from chronic wounds associated with diabetic ulcers, pressure ulcers, venous stasis ulcers and bums. In many cases the chronic wounds can take years to heal, have a high recurrence rate and for 54,000 patients a year, result in amputations. It is estimated that about 2.2 million patients in the United States have chronic ulcers that don't respond to conventional therapies. The wound healing market represents a large unmet need in terms of ethical wound healing agents. Maret has shown that angiotensin peptides can rapidly and effectively promote wound healing. In our phase I SBIR grant, we identified a compound (MARskinTM)(NorLeu3-A (1-7)), with superior properties in wound healing. In in vivo studies in different animal models of wound repair, NorLeu3-A (1-7) was superior to the only FDA approved drug to treat wound healing. These initial studies established NorLeu3-A (1-7) as our lead compound to develop as a wound-healing drug. In this phase II SBIR we will complete the preclinical studies needed to support the initiation of clinical trials with this drug. Specifically, we will test NorLeu3-A (1-7) in the Yucatan miniswine model, which is the industry standard animal model for establishing efficacy in wound repair. Furthermore, we will develop the most effective formulation of the compound for clinical trials, and will determine pharmacokinetics and safety of NorLeu3-A (1-7) for topical use. We will also investigate the molecular mechanisms of action of NorLeu3-A (1-7) in wound healing using DNA microarray and protein chip technologies. In Aim 2, we will develop a clinical protocol for NorLeu3-A (1-7) in wound healing, including recruitment of clinical investigators so that we can file an IND Exemption with the FDA for human testing in preparation for the initiation of Phase I safety and Phase II efficacy trials in the future. In addition to NorLeu3-A (1-7), six peptides were identified in our phase I SBIR studies that bound selectively to AT2 receptors, were evaluated in vivo and were shown to be promising tissue repair drug candidates. Because AT2 receptors are uniquely expressed in wound tissue, these peptides may have a high degree of specificity for wound healing not found with any other agents. In this phase II SBIR, these compounds will undergo extensive preclinical testing to determine whether they should be further developed as a second generation of wound healing drugs.